反应详情

(S)-4-(3-(N,N-Dibenzylaminomethyl)-3-fluoromethylpyrrolidin-1-yl)-2,3,5-trifluorobenzoyl chloride hydrochloride (0.97 g) was dissolved in acetonitrile (8 ml). Ethyl N,N-dimethylaminoacrylate (0.27 g) and triethylamine (0.4 g) were dissolved in acetonitrile (1 ml) and dropwise added thereto with stirring at room temperature. The mixture was stirred at room temperature for 1 hour and at 50° C. for 4 hours. The reaction mixture was cooled to room temperature and cyclopropylamine (0.11 g) was added. The mixture was stirred at room temperature for 3 hours and the reaction mixture was concentrated. Water was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. Dry dimethylformamide (3 ml) and potassium carbonate (0.26 g) were added to the residue, and the mixture was stirred at 60° C. for 8 hours. Water was added and the mixture was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The obtained oil was purified by silica gel column chromatography (developing solvent; chloroform:methanol=30:1) to give the object compound as a pale-yellow oil.

1. additiondropwise added
2. stirringThe mixture was stirred at room temperature for 1 hour and at 50° C. for 4 hours
3. temperatureThe reaction mixture was cooled to room temperature
4. stirringThe mixture was stirred at room temperature for 3 hours
5. concentrationthe reaction mixture was concentrated
6. additionWater was added to the residue
7. extractionthe mixture was extracted with ethyl acetate
8. washThe extract was washed with water
9. customdried
10. concentrationconcentrated
11. additionDry dimethylformamide (3 ml) and potassium carbonate (0.26 g) were added to the residue
12. stirringthe mixture was stirred at 60° C. for 8 hours
13. additionWater was added
14. extractionthe mixture was extracted with ethyl acetate
15. washThe extract was washed with water
16. customdried
17. concentrationconcentrated
18. customThe obtained oil was purified by silica gel column chromatography (developing solvent; chloroform:methanol=30:1)